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Ejection Fraction

  • change in ejection fraction, would expect a decline in EF of 2-3% per year, concerning if rapid progression, i.e., 10% decline or more - can we do absolute change? change this to 5% decline for 1 year

NTproBNP

  • % change over a period of time – a decrease is correlated with improvement, measured annually

SDTM Examples: Basic CMR Tests for Systolic Function

This section illustrates example analysis datasets for the following endpoints:

  • Percent change in ejection fraction over time (1 year)
  • Decline in ejection fraction over time (1 year) grouped by a decline greater than 10.0%
  • Percent change in NTproBNP over time (1 year)

Source Data

The SDTM examples used as the source data are from Section 2.1, Basic CMR Tests for Systolic Function. The CV dataset contains 16 rows, 1-8 for visit 1 and 9-16 for visit 6. Of these rows, the CVTESTCD = "LVEF_C" and CVTESTCD = "RVEF_C" representing the Ventricular Ejection Fraction, Calculated (%) for left and right were selected for the analysis. The LB dataset test where LBTESTCD = "BNPPRONT" was used to add the value of BNPPRONT to compute the percent change over time, and then it was added as a potential covariate in each row for the last analysis.

Example Analysis Datasets

The tables below show the analysis dataset metadata and parameters used for this example.

Analysis Datasets

The ADSL was combined with other SDTM datasets to create the analysis datasets. More than one SDTM dataset can be combined in this way. Also, stratification variables can be created in the ADSL to subset by, or to add variables needed in the analyses. For example, a flag (ACEMEDFL) could be added for ACE inhibitors. Another variable, body surface area (BSABL), was derived from the LB dataset at the baseline visit and added to ADSL.

The ADCVNTP dataset includes tests pertinent to these analyses. The records from LB where CVTESTCD is equal to "LVEF_C" or "RVEF_C" and LBTESTCD = "BNPPRONT" were selected. The relationship dataset RELREC illustrates the relationship between datasets. In this case, many lab draws may occur throughout the year, but only those linked to a specific visit are included. By subsetting the LB dataset with LBLNKID not missing, laboratory data that aligns with CV data can be filtered out and sorted using USUBJID and VISIT. If LBLNKID is not available, a windowing strategy could be used to select the laboratory draw closest to that visit for merging with CV, computed in AVISIT. In the example, only two LB records are shown which are linked to CV where CVTESTCD = "LVEF_C" or CVTESTCD = "R.VEF_C".

ADCVMR is an efficacy analysis dataset with only a few records for more complex modeling of changes in ejection fraction, plus the ProB-type test results. It is an ADaM Basic Data Structure (BDS) dataset, with additional variables added from ADCVNTP.

ADSL Analysis Dataset

This is a simplified example ADSL dataset; it is expected that additional variables for stratification or of interest for analysis would be included.

ADSL Variable Metadata

$titleHtml

adsl.xpt

RowSTUDYIDUSUBJIDBRTHDTTRTSDTTRT01PITTFLBSABASEACENHFL
1DMD-EFLGEDMD-EFLGE-10115FEB201315FEB2022Treatment AY0.65Y
$warningHtml

ADCVNTP Analysis Dataset

In this example, columns for derived variables BASE, CHG, PCHG and CHGCAT1 have been added to facilitate analyses of the efficacy endpoints. Specifically, example demographic data for ADSL were created for an 8 year old male. Also, a custom variable for BSA at baseline (BSABASE), and an example of a stratification variable for subjects with was added from ADSL.

Parameter Value List - ADCVNTP [ADCVNTP]

ADCVNTP Variable Metadata

Example 1 

This example dataset shows the findings and additional analysis variables associated with:

  • Left Ventricular Ejection Fraction, Calculated (%)
  • Right Ventricular Ejection Fraction, Calculated (%)
  • N-Terminal ProB-type Natriuretic Peptide (pg/mL)

Rows 1-2:Show the baseline ejection fraction measurements at VISIT 1.
Row 3:Shows the baseline N-Terminal ProB-type Natriuretic Peptide test results at VISIT 1.
Rows 4-5:Show the baseline ejection fraction measurements at VISIT 6.
Row 6:Shows the baseline N-Terminal ProB-type Natriuretic Peptide test results at VISIT 6.
$titleHtml

adcvntp.xpt

RowSTUDYIDUSUBJIDASEQBRTHDTTRT01PITTFLHEIGHTVWEIGHTVBSAACEINHFLPARAMPARAMCDPARAMNAVALAVISITAVISITNVISITADTABLFLBASECHGPCHGCHGCAT1SRCDOMSRCSEQ
1DMD-EFLGEDMD-EFLGE-101115FEB2013Treatment AY119201.09YLeft Ventricular Ejection Fraction, Calculated (%)LVEFC167Visit 1 (Baseline)1VISIT 116MAY2022Y67


CV3
2DMD-EFLGEDMD-EFLGE-101215FEB2013Treatment AY119201.09YRight Ventricular Ejection Fraction, Calculated (%)RVEFC274Visit 1 (Baseline))1VISIT 116MAY2022Y74


CV7
3DMD-EFLGEDMD-EFLGE-101315FEB2013Treatment AY119201.09YN-Terminal ProB-type Natriuretic Peptide (IU/L)BNPPRONT340Visit 1 (Baseline)1VISIT 116MAY2022Y40


LB1
4DMD-EFLGEDMD-EFLGE-101415FEB2013Treatment AY13232 1.33YLeft Ventricular Ejection Fraction, Calculated (%)LVEFC160Visit 6 (1 Year)6VISIT 606APR2023
67-7-10.447761Decline >=10.0CV11
5DMD-EFLGEDMD-EFLGE-101515FEB2013Treatment AY132321.33YRight Ventricular Ejection Fraction, Calculated (%)RVEFC261Visit 6 (1 Year)6VISIT 606APR2023
74-13-17.567568Decline >=10.0CV15
6DMD-EFLGEDMD-EFLGE-101615FEB2013Treatment AY132321.33YN-Terminal ProB-type Natriuretic Peptide (IU/L)BNPPRONT3900Visit 6 (1 Year)6VISIT 106APR2023
408602,150
LB2

Dataset Debug Message

There is a leading, trailing, or non-breaking space in the dataset.

Dataset Wrapper Debug Message

Please add a row column to your dataset.


Example 2

The dataset above can also be set up to provide multivariate analyses by taking the lab tests of interest, transposing and merging with the ADCVNTP dataset. In that case, the records from LB are not needed as a row. The stratification variables such as BSA and ACEINHFL are carried over, but not HEIGHTW or WEIGHTW which were used to compute BSA values.

Parameter Value List - ADCVCMR [ADCVCMR]

$titleHtml

adcvcmr.xpt

RowSTUDYIDUSUBJIDASEQBRTHDTTRT01PITTFLBSAACEINHFLBNPPRONTBNPCHGPARAMPARAMCDPARAMNAVALAVISITAVISITNVISITADTABLFLBASECHGPCHGSRCDOMSRCSEQ
1DMD-EFLGEDMD-EFLGE-101115FEB2013Treatment AY1.09Y40
Left Ventricular Ejection Fraction, Calculated (%)LVEFC167Visit 1 (Baseline)1VISIT 116MAY2022Y67

CV3
2DMD-EFLGEDMD-EFLGE-101215FEB2013Treatment AY1.09Y40
Right Ventricular Ejection Fraction, Calculated (%)RVEFC274Visit 1 (Baseline)1VISIT 116MAY2022Y74

CV7
3DMD-EFLGEDMD-EFLGE-101315FEB2013Treatment AY 1.33Y9002150Left Ventricular Ejection Fraction, Calculated (%)LVEFC160Visit 6 (1 Year)6VISIT 606APR2023
67-7-10.447761CV11
4DMD-EFLGEDMD-EFLGE-101415FEB2013Treatment AY1.33Y9002150Right Ventricular Ejection Fraction, Calculated (%)RVEFC261Visit 6 (1 Year)6VISIT 606APR2023
74-13-17.567568CV15

Dataset Debug Message

There is a leading, trailing, or non-breaking space in the dataset.

Example Analysis Results Metadata (ARM) Tables

For more details on ARM, see the ADaMIG and the Analysis Results Metadata (ARM) v1.0 for Define-XML v2.0 (https://www.cdisc.org/standards/foundational/adam).

Table 1. A simple comparison of change by treatment groups over one year.

Display

Table 14.xx.xx Change in Left Ventricular Ejection Fraction Percent Over 1 Year

Analysis ResultComparison of Percent Change of Ejection Fraction for the Treatment Groups (1 Year)
Analysis Variables(s)CHG
Analysis ReasonPrimary efficacy endpoint as prespecified in the SAP
Analysis PurposePrimary outcome measure

Data References

(incl. selection criteria)

PARAMCD = "LVEFC"

Where ITTFL = "Y" and AVISITN = 6;

Documentation

Comparison of Means with 95% confidence interval

Programming Statements 

(Add programming language statements here: SAS, R, etc.)

/* Subset the data */

DATA ONE;

SET ADCVCMR;

Where ITTFL = "Y" and AVISITN = 2 and PARAMCD = "LREF";

RUN;

PROC MEANS DATA=ONE MEAN STD MEDIAN ;

CLASS TRT01P;

VAR CHG;  /*  Could add RVEF here as well */

RUN;


Table 2. This table demonstrates a model over multiple time points, adding some of the covariates that were retained in the analysis dataset. 


Display

Table 14.xx.xx Percent Change in Left Ventricular Ejection Fraction Percent Over Time (Yearly)

Analysis ResultComparison of Percent Change of Ejection Fraction for the Treatment Groups Over Time ( yearly)
Analysis Variables(s)CHG
Analysis ReasonPrimary efficacy endpoint as prespecified in the SAP
Analysis PurposePrimary outcome measure

Data References

(incl. selection criteria)

PARAMCD = "LVEFC"

Where ITTFL = "Y"

Documentation

 The mixed model using lsmeans to compare treatment groups

Programming Statements 

(Add programming language statements here: SAS, R, etc.)

/* Note that CHG is only computed post-baseline, so subset for the yearly visits, i.e. 6, 12, 18 etc. */

DATA TWO;

SET ADCVCMR;

/* Subset by param, as there are two parameters with CHG calculated*/

Where ITTFL = "Y" and AVISITN IN(6,12,18,24,36,48)  and PARAMCD = "LVEFC"; 

RUN;


PROC MIXED DATA=ADCVNTP;

CLASS STUYDID TRT01P AVISITN;

MODEL PCHG=AVISITN*TRT01P/Solution;

RANDOM INTERCEPT / SUBJECT=STUYDID TYPE=UN;

LSMEANS TRT01P*AVISITN/ CL PDIFF;

RUN;

Table 3.  This example uses the dataset ADCVNTP, selecting for the parameter "N-Terminal ProB-type Natriuretic Peptide (IU/L)".

Display

Table 14.xx.xx Percent change in NTproBNP over 1 Year

Analysis ResultComparison of Percent Change of NTproBNP for the Treatment Groups Over a period of time.
Analysis Variables(s)PCHG
Analysis ReasonPrimary efficacy endpoint as prespecified in the SAP
Analysis PurposePrimary outcome measure

Data References

(incl. selection criteria)

PARAMCD = "BNPPRONT"

Where ITTFL = "Y" AND AVISIT GE 6;

Documentation

 The mixed model using lsmeans to compare treatment groups

Programming Statements 

(Add programming language statements here: SAS, R, etc.)

/* NEEDS UPDATING*/

PROC MEANS DATA=ADCVCMR MEAN STD MEDIAN maxdec=3;

CLASS TRT01P;

BY VISIT;

VAR BNPPRONT;  

RUN;

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